Evaluation of the effect of dextromethorphan and meloxicam in preventing vincristine-induced neuropathy in mice

Abstract

Introduction: Mechanisms including oxidative stress, increased activity of glutamate receptors and increased activity of serotonin receptors have been proposed in the process of neuropathy caused by anticancer drugs. Anti-inflammatory and antioxidant effects have been proposed for meloxicam and antioxidant effects for dextromethorphan.Goal: The study aimed to investigate the preventive effect of meloxicam and dextromethorphan on neuropathic pain caused by vincristine in mice.Materials and methods: 90 male mice in the weight range of 25-35 grams were divided into 10 groups of 9 and were subjected to the following treatment regimens for 21 days;Three doses of meloxicam (SC, 0.5, 1, 2 mg/kg) and dextromethorphan (10, 20, 40 mg/kg, SC) were injected twice a day for 21 days. On the eighth to the seventeenth day, for 10 days, vincristine injection (IP, 0.1 mg/kg) was administered half an hour after the injection of drugs. On days 0-8-11-15-18-22, the hot plate test was done. At the end of the 22nd day, blood was taken from the hearts of animals to perform MDA and TAC tests.Result: The results indicated a preventive effect of certain doses of dextromethorphan (10, 20, 40 mg/kg, SC) and meloxicam (SC, 0.5 mg/kg) in vincristine-induced neuropathy. However the simultaneous use of these two drugs did not improve neuropathy. Changes in TAC and MDA serum levels were also not as expected.Conclusion: Certain doses of dextromethorphan (10, 20, 40 mg/kg) and meloxicam (0.5 mg/kg) can effectively prevent neuropathy caused by vincristine. Dextromethorphan inhibits vincristine-induced neuropathy in a dose-dependent manner, while meloxicam does not. The results of TAC and MDA serum levels were not consistent with the results of drugs in the prevention of vincristine-induced neuropathy; Therefore, mechanisms other than oxidative stress seem to be effective in preventing neuropathy caused by vincristine, and finding the mechanism requires additional studies.